AIDS (acquired immunodeficiency syndrome) is one of the leading causes of death in the developing world. HIV-1, a retrovirus which is a member of the lentivirus subfamily, is the etiologic agent of AIDS. The Lentiviridae include non-oncogenic retroviruses which usually infect cells of the immune system, particularly macrophages and T cells, causing persistent infections in diseases with long incubation periods and cytopathic effects in infected cells, such as syncytia and cell death. Lentiviral infections are not cleared by the immune system, and lead to accumulated immunologic damage over a period of many years.
HIV-1 comprises an RNA genome and exhibits reverse transcriptase activity. During its growth cycle, HIV-1 copies its RNA into proviral DNA, which is able to integrate into the chromosomal DNA of the host cell (provirus). Due to its retroviral nature and the small size of its genome, HIV-1 replication is strongly dependent on the host's cell machinery. Thus, HIV uses the transcriptional and translational machinery of the host to express viral RNA and proteins and ultimately to release mature viruses from the cell by budding from the cytoplasmic membrane. Viral replication of HIV-1 results in the death of host's helper T cells, which leads to a state of severe immunodeficiency (AIDS), to the development of various malignancies and opportunistic infections, and ultimately to the death of the infected organism.
HIV-1 is capable of infecting human host cells both through free viral particles and through cell-to-cell transmission [1, 2]. Cell-to-cell spread is up to 10,000 times more efficient than free viral infection, because virus is shielded from cellular and immunological barriers [3, 4, 5]. Several distinct modes of cell-to-cell HIV-1 dissemination have been reported, including virological synapses (VS) [6, 7], syncytia [8], filopodial bridges [9], and nanotubes [10].
Accordingly, the results presented herein elucidate certain of the mechanisms involved in cell-to-cell transmission of HIV-1.
The citation of references herein shall not be construed as an admission that such is prior art to the present invention.
Several publications and patent documents are referenced in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these publications and documents is incorporated by reference herein.